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Novel site‐specific systemic delivery of Rapamycin with perfluorobutane gas microbubble carrier reduced neointimal formation in a porcine coronary restenosis model
Author(s) -
Kipshidze Nicholas N.,
Porter Thomas R.,
Dangas George,
Yazdi Hamid,
Tio Fermin,
Xie Feng,
Hellinga David,
Wolfram Roswitha,
Seabron Rufus,
Waksman Ron,
Abizaid Alexander,
Roubin Gary,
Iyer Sriram,
Colombo Antonio,
Leon Martin B.,
Moses Jeffrey W.,
Iversen Patrick
Publication year - 2005
Publication title -
catheterization and cardiovascular interventions
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.988
H-Index - 116
eISSN - 1522-726X
pISSN - 1522-1946
DOI - 10.1002/ccd.20285
Subject(s) - restenosis , medicine , coronary arteries , perfusion , stent , western blot , cardiology , artery , urology , chemistry , biochemistry , gene
Earlier studies demonstrated that perfluorobutane gas microbubble carrier (PGMC) adheres to injured arteries and enhances the drug uptake specifically into the cells of the denuded vessel segment. The purpose of this study was to investigate the effect of PGMC‐based systemic delivery of Rapamycin on expression of p27 in vascular tissue and restenosis in porcine coronary arteries after stent implantation. Eight pigs underwent coronary stent implantation (three stents per animal). Five pigs were treated with i.v. injection of PGMC with 2 mg of Rapamycin and three animals served as control. Four hours postprocedure, three pigs were sacrificed and stented segments were analyzed by high‐performance liquid chromatography (HPLC) and Western blot. In chronic experiments, five pigs (15 stent sites) were sacrificed at 28 days following intervention and vessels were perfusion‐fixed. HPLC of the treated arteries demonstrated high drug concentration in the vessel tissue, and Western blot analysis showed elevated expression of p27 at 4 hr postprocedure. Histomorphometry revealed significantly reduced (by 40%) neointimal formation in the PGMC/Rapamycin group compared with controls (1.84 ± 0.84 vs. 4.77 ± 1.71 mm 2 , respectively; P < 0.001). In the porcine coronary model, site‐specific systemic delivery of Rapamycin utilizing PGMC resulted in overexpression of p27 and a significant reduction of neointimal formation within the stented segments. Catheter Cardiovasc Interv 2005;64:389–394. © 2005 Wiley‐Liss, Inc.